Progesterone receptor expression contributes to gemcitabine resistance at higher ECM stiffness in breast cancer cell lines

Grant, Emma K.; Bucklain, Fatma A.; Ginn, Lucy; Laity, Peter R.; Ciani, Barbara; Bryant, Helen E.

doi:10.1371/journal.pone.0268300

Cited by 4 publications

(2 citation statements)

References 26 publications

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“… 30 PR expression is beneficial to the resistance of BC cells to gemcitabine. 31 Then, we included hsa-miR-3646, hsa-miR-4741, hsa-miR-6730-3p, hsa-miR-6831-5p, hsa-miR-8485, nation, ER ratio and PR ratio for the multivariate logistic regression analysis and the development of the nomogram model. The nomogram model has potential predictive values and practical implications in BC.…”

Section: Discussionmentioning

confidence: 99%

Predictive miRNAs Patterns in Blood of Breast Cancer Patients Demonstrating Resistance Towards Neoadjuvant Chemotherapy

Fan¹,

Tang²,

Wang³

et al. 2023

BCTT

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Objective The effect of chemotherapy in patients with breast cancer (BC) is uncertain. This study attempted to analyze serum microRNAs (miRNAs) in NAC resistant and sensitive BC patients and develop a miRNA-based nomogram model. To further help clinicians make treatment decisions for hormone receptor-positive patients. Methods A total of 110 BC patients with NAC were recruited and assigned in sensitive and resistant group, and 4 sensitive patients and 3 resistant patients were subjected to high-throughput sequencing. The functions of their target genes were analyzed by GO and KEGG. Five BC-related reported miRNAs were selected for expression pattern measurement by RT-qPCR and multivariate logistic analysis. The nomogram model was developed using R 4.0.1, and its predictive efficacy, consistency and clinical application value in development and validation groups were evaluated using ROC, calibration and decision curves. Results There were 44 differentially-expressed miRNAs in resistant BC patients. miR-3646, miR-4741, miR-6730-3p, miR-6831-5p and miR-8485 were candidate for resistance diagnosis in BC. Logistic multiple regression analysis showed that miR-4741 (or = 0.30, 95% CI = 0.08–0.63, P = 0.02) and miR-6831-5p (or = 0.48, 95% CI = 0.24–0.78, P = 0.01) were protective factors of BC resistance. The ROC curves showed a sensitivity of 0.884 and 0.750 for miR-4741 and miR-6831-5P as markers of resistance, suggesting that they can be used as independent risk factors for BC resistance. The other 3 miRNAs can be used as calibration factors to establish the risk prediction model of resistance in BC. In risk model, the prediction accuracy of resistance of BC is about 78%. 5-miRNA signature diagnostic models can help clinicians provide personalized treatment for NAC resistance BC patients to improve patient survival. Conclusion MiR-4741 and miR-6831-5p are independent risk factors for breast cancer resistance. This study constructed a nomogram model of NAC resistance in BC based on 5 differentially-expressed serum miRNAs.

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Section: Discussionmentioning

confidence: 99%

Predictive miRNAs Patterns in Blood of Breast Cancer Patients Demonstrating Resistance Towards Neoadjuvant Chemotherapy

Fan¹,

Tang²,

Wang³

et al. 2023

BCTT

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“…The physics of cancer is an emerging field of oncology which highlights the mechanical properties of the tumor microenvironment (TME), focusing on the role of cell-ECM interactions in cancer disease and metastasis ( Burgos-Panadero, Lucantoni, et al, 2019 ; Grant et al, 2022 ; Kpeglo et al, 2022 ; Liu et al, 2022 ; Xiao et al, 2022 ). As glycoproteins interact with integrins and are involved in cell adhesion and migration pathways, molecules similar to VN, such as FN have been used in cancer mechanotransduction studies ( Missirlis and Spatz, 2014 ; Elosegui-Artola et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

Vitronectin-based hydrogels recapitulate neuroblastoma growth conditions

Monferrer

Dobre

Trujillo

et al. 2022

Front. Cell Dev. Biol.

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The tumor microenvironment plays an important role in cancer development and the use of 3D in vitro systems that decouple different elements of this microenvironment is critical for the study of cancer progression. In neuroblastoma (NB), vitronectin (VN), an extracellular matrix protein, has been linked to poor prognosis and appears as a promising therapeutic target. Here, we developed hydrogels that incorporate VN into 3D polyethylene glycol (PEG) hydrogel networks to recapitulate the native NB microenvironment. The stiffness of the VN/PEG hydrogels was modulated to be comparable to the in vivo values reported for NB tissue samples. We used SK-N-BE (2) NB cells to demonstrate that PEGylated VN promotes cell adhesion as the native protein does. Furthermore, the PEGylation of VN allows its crosslinking into the hydrogel network, providing VN retention within the hydrogels that support viable cells in 3D. Confocal imaging and ELISA assays indicate that cells secrete VN also in the hydrogels and continue to reorganize their 3D environment. Overall, the 3D VN-based PEG hydrogels recapitulate the complexity of the native tumor extracellular matrix, showing that VN-cell interaction plays a key role in NB aggressiveness, and that VN could potentially be targeted in preclinical drug studies performed on the presented hydrogels.

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Progesterone receptor potentiates macropinocytosis through CDC42 in pancreatic ductal adenocarcinoma

Liao,

Gai,

Qian

et al. 2024

Oncogenesis

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Endocrine receptors play an essential role in tumor metabolic reprogramming and represent a promising therapeutic avenue in pancreatic ductal adenocarcinoma (PDAC). PDAC is characterized by a nutrient-deprived microenvironment. To meet their ascendant energy demands, cancer cells can internalize extracellular proteins via macropinocytosis. However, the roles of endocrine receptors in macropinocytosis are not clear. In this study, we found that progesterone receptor (PGR), a steroid-responsive nuclear receptor, is highly expressed in PDAC tissues obtained from both patients and transgenic LSL-KrasG12D/+; LSL-Trp53R172H/+; PDX1-cre (KPC) mice. Moreover, PGR knockdown restrained PDAC cell survival and tumor growth both in vitro and in vivo. Genetic and pharmacological PGR inhibition resulted in a marked attenuation of macropinocytosis in PDAC cells and subcutaneous tumor models, indicating the involvement of this receptor in macropinocytosis regulation. Mechanistically, PGR upregulated CDC42, a critical regulator in macropinocytosis, through PGR-mediated transcriptional activation. These data deepen the understanding of how the endocrine system influences tumor progression via a non-classical pathway and provide a novel therapeutic option for patients with PDAC.

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Progesterone receptor expression contributes to gemcitabine resistance at higher ECM stiffness in breast cancer cell lines

Cited by 4 publications

References 26 publications

Predictive miRNAs Patterns in Blood of Breast Cancer Patients Demonstrating Resistance Towards Neoadjuvant Chemotherapy

Predictive miRNAs Patterns in Blood of Breast Cancer Patients Demonstrating Resistance Towards Neoadjuvant Chemotherapy

Vitronectin-based hydrogels recapitulate neuroblastoma growth conditions

Progesterone receptor potentiates macropinocytosis through CDC42 in pancreatic ductal adenocarcinoma

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